Prospective study of cancer survival in patients with HuD-antibody-associated paraneoplastic neurological disorders

The appearance of a paraneoplastic neurological disorder (PND) with Hu-antibodies, often before tumour detection, together with spontaneous tumour regression in a few patients, suggests that immune responses to HuD, possibly mediated by cytotoxic T-cells, could be beneficial to the patient.1 Nevertheless, in previous retrospective studies, survival in Hu-antibody-associated PNDs (Hu-Ab/PNDs) in general was similar to those in patients with small-cell lung cancer (SCLC) without neurological illness.2 3\n\nHere we studied, for the first time prospectively, tumour outcomes in a large series of patients with Hu-Ab/PNDs, comparing with contemporaneous patients with SCLC without neurological symptoms.\n\n### Patients\n\nWritten consent was obtained from all patients. From July 2012 to June 2015 prospectively we collected all serum samples that were positive for Hu-antibodies at Oxford University Hospitals as part of routine diagnostic testing via referral from any of England’s 152 acute hospital trusts. Diagnostic categorisation of associated PNDs was agreed between the research team and the referring physician, in line with published diagnostic criteria.4 For survival comparisons, contemporaneous control data and pre-treatment serum samples were obtained prospectively from 245 patients with SCLC, without PNDs, from the Nottingham Trent region over the same time period. Serum samples were stored at −80°C and retested for Hu and SOX2 antibodies by ELISA, and paraneoplastic antibodies tested on frozen rat cerebellum with positive results confirmed using a multi-line blot (Ravo Diagnostika, Freiburg, Germany) (see online supplemental methods).\n\n### Supplementary data\n\n[jnnp-2021-326067supp001.pdf]\n\n### Statistical analysis\n\nSurvival statistics from date of SCLC diagnosis in PND and control groups were calculated using log-rank tests, and differences in cancer survival according to presence of PNDs and Hu-antibodies were evaluated using a Cox proportional hazards model.\n\n### Patients with Hu-antibody PNDs and SCLC controls\n\nOne …